The principal goals of the proposal are two-fold: (1) To study the effects of alcohol on hepatic collagen metabolism in animals and in man, and (2) to investigate factors responsible for change in hepatic alcohol dehydrogenase activity and their physiological significance. In animals, the effect of various periods of ethanol feeding will be determined on parameters of hepatic collagen synthesis, deposition, and degradation. In addition, the effect of ethanol feeding on the mineral and collagen composition of bone will be studied, to determine whether or not bone is a significant source of the increased urinary excretion of hydroxyproline and glycosaminoglycans previously demonstrated after ethanol feeding. In patients with alcoholic liver disease, the activity of hepatic collagen proline hydroxylase and the urinary excretion of hydroxyproline and glycosaminoglycans will continue to be determined as parameters reflecting collagen synthesis and degradation respectively. Also, the effect of D-penicillamine on these parameters will be studied in patients with alcoholic hepatitis. Experimentally-induced uremia will be used initially as a model to study the enzymatic characteristics and the factors responsible for increases in hepatic alcohol dehydrogenase activity. Possible changes in the affinity of increased enzyme activity for two physiological substrates, vitamin A and farnesol, and the effect of ethanol in vitro on the oxidation of the physiological substrates by the enzyme, will be investigated. The possible mediation of increase in alcohol dehydrogenase activity by hormones will be explored. Thereafter the effects of some hormones and physiological stress on hepatic alcohol dehydrogenase activity and on rates of ethanol elimination from the blood will be studied.